Stepping out of the flow: capillary extravasation in cancer metastasis

In order for cancer cells to successfully colonize a metastatic site, they must detach from the primary tumor using extracellular matrix-degrading proteases, intravasate and survive in the circulation, evade the immune response, and extravasate the vasculature to invade the target tissue parenchyma, where metastatic foci are established. Though many of the steps of metastasis are widely studied, the precise cellular interactions and molecular alterations associated with extravasation are unknown, and further study is needed to elucidate the mechanisms inherent to this process. Studies of leukocytes localized to inflamed tissue during the immune response may be used to elucidate the process of cancer extravasation, since leukocyte diapedesis through the vasculature involves critical adhesive interactions with endothelial cells, and both leukocytes and cancer cells express similar surface receptors capable of binding endothelial adhesion molecules. Thus, leukocyte extravasation during the inflammatory response has provided a model for transendothelial migration (TEM) of cancer cells. Leukocyte extravasation is characterized by a process whereby rolling mediated by cytokine-activated endothelial selectins is followed by firmer adhesions with beta1 and beta2 integrin subunits to an activated endothelium and subsequent diapedesis, which most likely involves activation of Rho GTPases, regulators of cytoskeletal rearrangements and motility. It is controversial whether such selectin-mediated rolling is necessary for TEM of cancer cells. However, it has been established that similar stable adhesions between tumor and endothelial cells precede cancer cell transmigration through the endothelium. Additionally, there is support for the preferential attachment of tumor cells to the endothelium and, accordingly, site-specific metastasis of cancer cells. Rho GTPases are critical to TEM of cancer cells as well, and some progress has been made in understanding the specific roles of the Rho GTPase family, though much is still unknown. As the mechanisms of cancer TEM are elucidated, new approaches to study and target metastasis may be utilized and developed.     

Correlation of Changes in Leukocytes Levels 24 Hours after Intravenous Thrombolysis With Prognosis in Patients With Acute Ischemic Stroke

Objective

Leukocytes play a crucial role in inflammation and immune response. This study aims to demonstrate the value of changes in leukocytes levels 24 hours after intravenous thrombolysis to predict prognosis in acute ischemic stroke (AIS).

妊娠高血压综合征患者外周血单个核细胞产生Th1、Th2型细胞因子失衡的研究

目的　研究妊娠高血压综合征 (简称妊高征 )患者外周血单个核细胞 (peripheral bloodmononuclear cell,PBMC)产生 Th1、Th2型细胞因子的功能变化。　方法　妊高征组 4 3例 ,正常孕妇组 15例 ,健康非孕组 15例 ,采用 EL ISA方法检测外周血 PBMC体外培养上清液中白细胞介素 2(interleukin- 2 ,IL- 2 )、干扰素 γ(interferon- γ,IFN- γ)及白细胞介素 4 (interleukin- 4 ,IL- 4 )水平。　结果　 PBMC体外培养上清液中 ,IL- 2在正常妊娠组为 (14 0 .3± 73.2 ) ng/ L,与健康非孕组 (2 5 9.5± 114 .4 ) ng/ L 相比水平下降 (P<0 .0 1) ;在妊高征组为 (2 34.6± 10 7.2 ) ng/ L,与正常妊娠组相比水平升高 (P<0 .0 1)。IFN- γ在正常妊娠组为 (30 7.5± 10 6 .4 ) ng/ L,与健康非孕组 (4 83.7± 177.8) ng/ L相比水平下降 (P<0 .0 1) ;在妊高征组为 (4 13.5± 14 9.7) ng/ L,与正常妊娠组相比水平升高 (P<0 .0 1)。IL- 4在正常妊娠组为 (4 1.9± 11.4 ) ng/ L,与健康非孕组 (2 7.4± 8.3) ng/ L 相比水平升高 (P<0 .0 0 1) ;在妊高征组为 (32 .1± 12 .0 ) ng/ L,与正常妊娠组相比水平下降 (P<0 .0 1)。IL- 2 / IL- 4比值在正常妊娠组为 3.5± 1.9,与健康非孕组 10 .1± 4 .8相比比值下降 (P<0 .0 0 1) ;在     

郑州地区183例临床输血不良反应回顾性分析

目的 分析本地区不同血液制品的输血不良反应发生率的情况,为血站采用血液制品精细化管理来有效预防输血不良反应提供理论依据。方法 统计2017年1~12月河南省红十字血液中心发放至郑州市签订供血合同医院的各类血液制品,收集并查阅同期医院反馈的183例临床输血反应反馈单,记录血液制品种类和输血不良反应类型,比较不同血液制品不良反应的发生率,统计分析不同血液制品引起输血不良反应类型的差异。结果 2017年1~12月共发放血液制品751 490袋,发生输血反应183例,输血不良反应总发生率0.024%（183/751 490）,其中全血、悬浮红细胞、去白悬浮红细胞、普通冰冻血浆和病毒灭活血浆的不良反应发生率分别为1.869%（2/107）、0.052%（89/172 366）、0.024%（15/62 247）、0.030%（47/155 337）和0.005%（7/147 460）。输血不良反应以过敏和发热为主,过敏的患者中,由普通冰冻血浆引起的输血反应38例（40.43%）高于病毒灭活血浆6例（6.38%）,差异有统计学意义（P<0.05）;发热的患者中,由悬浮红细胞引起的输血反应54例（75.00%）高于去白悬浮红细胞6例（8.33%）,差异有统计学意义（P<0.05）。结论 全血的输血不良反应发生率最高,其次为悬浮红细胞和普通冰冻血浆;去白悬浮红细胞和病毒灭活血浆可以显著减少输血不良反应的发生率。     

Pleiotropy within gene variants associated with nonalcoholic fatty liver disease and traits of the hematopoietic system

Genome-wide association studies of complex diseases, including nonalcoholic fatty liver disease (NAFLD), have demonstrated that a large number of variants are implicated in the susceptibility of multiple traits — a phenomenon known as pleiotropy that is increasingly being explored through phenome-wide association studies. We focused on the analysis of pleiotropy within variants associated with hematologic traits and NAFLD. We used information retrieved from large public National Health and Nutrition Examination Surveys, Genome-wide association studies, and phenome-wide association studies based on the general population and explored whether variants associated with NAFLD also present associations with blood cell-related traits. Next, we applied systems biology approaches to assess the potential biological connection/s between genes that predispose affected individuals to NAFLD and nonalcoholic steatohepatitis, and genes that modulate hematological-related traits—specifically platelet count. We reasoned that this analysis would allow the identification of potential molecular mediators that link NAFLD with platelets. Genes associated with platelet count are most highly expressed in the liver, followed by the pancreas, heart, and muscle. Conversely, genes associated with NAFLD presented high expression levels in the brain, lung, spleen, and colon. Functional mapping, gene prioritization, and functional analysis of the most significant loci (P < 1 × 10^-8) revealed that loci involved in the genetic modulation of platelet count presented significant enrichment in metabolic and energy balance pathways. In conclusion, variants in genes influencing NAFLD exhibit pleiotropic associations with hematologic traits, particularly platelet count. Likewise, significant enrichment of related genes with variants influencing platelet traits was noted in metabolic-related pathways. Hence, this approach yields novel mechanistic insights into NAFLD pathogenesis.